title: RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis.
abstract: To date, RNase degradation and endosome/lysosome trapping are still serious problems for siRNA-based molecular therapy, although different kinds of delivery formulations have been tried. In this report, a cell penetrating peptide (CPP, including a positively charged segment, a linear segment, and a hydrophobic segment) and a single wall carbon nanotube (SWCNT) are applied together by a simple method to act as a siRNA delivery system. The siRNAs first form a complex with the positively charged segment of CPP via electrostatic forces, and the siRNA-CPP further coats the surface of the SWCNT via hydrophobic interactions. This siRNA delivery system is non-sensitive to RNase and can avoid endosome/lysosome trapping in vitro. When this siRNA delivery system is studied in Hela cells, siRNA uptake was observed in 98% Hela cells, and over 70% mRNA of mammalian target of rapamycin (mTOR) is knocked down, triggering cell apoptosis on a significant scale. Our siRNA delivery system is easy to handle and benign to cultured cells, providing a very efficient approach for the delivery of siRNA into the cell cytosol and cleaving the target mRNA therein.
authors.affiliation: Department of Anatomy, Key Laboratory of Construction and Detection of Guangdong Province, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Xinglu
authors.initials: X
authors.lastname: Jiang
authors.forename: Guobao
authors.initials: G
authors.lastname: Wang
authors.forename: Ru
authors.initials: R
authors.lastname: Liu
authors.forename: Yaling
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Qiu
authors.forename: Xueyun
authors.initials: X
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D004705:Endocytosis; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D055672:Static Electricity; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; D012260:Ribonucleases